A number of laboratory and clinical procedures require the use of an array of wells or tubes in which multiple samples are placed for analysis, cell growth, amplification, isolation or other purposes. In general, conventional multi-well plates and tube arrays (non-filtration type) have a single opening at the top through which samples are added or removed.
An important disadvantage in the use of arrays of tubes mounted within a plate, and with multi-well plates (either with or without a filtration feature) is the problem associated with contamination of the samples. Most laboratory protocols must be performed with a high degree of stringency in terms of limiting contamination of the samples. When multiple samples are processed in a confined area, such as an 8.times.12 or 4.times.6 format, strip wells (in strips of 8 or 12 wells), or in any format with multiple sample containers in a small area, the risk of cross-contamination of samples is significant, giving rise to erroneous results. If a single unitary plate (as currently available) is used as a collective lid to cover the tops of all the wells or tubes, the lack of a seal could allow the migration of samples between wells or tubes during handling, or simply through condensation and capillary processes. Tapes which are used currently to seal the tops of the wells are not very reliable. Adhesive tapes limit the number of conditions that the plate can be subjected to (efficient boiling, freeze-thawing and vortexing the plate are difficult without causing cross-contamination) and heat sealing tape requires specialized heat-sealing equipment. Incorporation of a tape sealing process in automated systems would be difficult. In addition, multi-well or tube arrays which utilize individual stoppers are unwieldy and allow the introduction of contaminants as the reagents and the like are added to the wells/tubes. This problem of cross-contamination is particularly acute when tight fitting caps and tape are opened, which frequently results in aerosol formation. These aerosols, in addition to being a potential source of cross-contamination, may also be hazardous to the operator.
A problem often encountered with cell culture procedures is the contamination of the cultures by microorganisms from the environment or the atmosphere. This problem has been difficult to overcome, because cell-culture procedures often require the microorganisms to be grown in, a controlled atmosphere (such as 5% carbon dioxide); the conventional plates therefore have a loose fitting lid to reduce evaporation while allowing gas exchange and yet minimizing contamination. Also, it would not be possible to clamp the lid to the multi-well plate without changing the dimensions of the plate, which would make it difficult to use with existing instruments such as plate readers, centrifuges and the like. It is important to appreciate that the use of the membrane in the present invention is very different from prior art involving 96-well filtration devices, where the liquid samples have to come in contact with the membrane for the purpose of filtration. Thus, in the prior art, the membrane provides for flow-through of liquid, with the liquid often in contact with the membrane for prolonged periods of time prior to filtration. In the present invention the membrane prevents flow-through of non-gaseous materials, but allows gas-exchange.
Conventional glass microscope slides having one or more wells are now being used as sample holders for in situ nucleic acid amplification techniques such as PCR. Generally, either glue or cosmetic nail enamel is used to stick the cover directly to the slide, requiring the use of heat or a solvent to remove the cover.
Therefore, it is an object of the present invention to provide a plate/tray assembly having an array of sample containment site, which are designed to reduce the risk of cross-contamination between containment sites.
It is another object of the present invention to provide a multi-well plate or tube array in which cross-contamination of samples is significantly reduced by providing a resilient gasket which isolates each containment site.
It is yet another object of the present invention to have a tube array (or multi-well plate) which can be sealed without the use of a gasket or tight fit caps.
It is a further object of the present invention to provide a method of leaving samples in the sample containment sites in the multi-well plate/tube array open to the atmosphere and yet sealed from microbial, particulate or other contamination from atmospheric sources.
It is still a further object of the present invention to provide a sample containment assembly of multiple samples (such as 96 well plates and cluster plates) which can be hermetically sealed and clamped together without changing the effective dimensions of the assembly so that standardized equipment such as automated well washers, automated scanning instruments and centrifuges can still be used.
Finally, it is still a further object of the present invention to provide a sealing system for glass or plastic slides, which can be used without gluing the cover slip to the slide.